Assessment of risk factors for acute graft- versus-host disease post-hematopoietic stem cell transplantation: a retrospective study based on a proportional odds model using a nonlinear mixed-effects model

Ling Xue; Lin Song; Xun Yu; Xiao Yang; Fan Xia; Xiaoliang Ding; Chenrong Huang; Depei Wu; Liyan Miao

doi:10.1177/20406207231205406

Assessment of risk factors for acute graft- versus-host disease post-hematopoietic stem cell transplantation: a retrospective study based on a proportional odds model using a nonlinear mixed-effects model

Ther Adv Hematol. 2023 Oct 21:14:20406207231205406. doi: 10.1177/20406207231205406. eCollection 2023.

Authors

Ling Xue^{1

2}, Lin Song^{1

3}, Xun Yu¹, Xiao Yang⁴, Fan Xia¹, Xiaoliang Ding¹, Chenrong Huang¹, Depei Wu⁵, Liyan Miao⁶

Affiliations

¹ Department of Pharmacy, The First Affiliated Hospital of Soochow University, Suzhou, China.
² Department of Pharmacology, Faculty of Medicine, University of the Basque Country - (UPV/EHU), Leioa, Spain.
³ College of Pharmaceutical Sciences, Soochow University, Suzhou, China.
⁴ National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China.
⁵ National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, No. 188, Shizi Street, Suzhou 215006, China.
⁶ Department of Pharmacy, The First Affiliated Hospital of Soochow University, No. 899, Pinghai Road, Suzhou 215006, China.

Abstract

Background: Acute graft-versus-host disease (aGVHD) is a major complication following hematopoietic stem cell transplantation (HSCT).

Objective: This study aimed to explore the risk factors for the incidence of aGVHD in patients post-HSCT.

Design: This was a retrospective study.

Methods: A total of 407 patients were enrolled. The patients' data were recorded from the medical records. The exposure of cyclosporine was estimated based on a population pharmacokinetics model. The occurrence of aGVHD was clinically graded and staged in severity from grades I to IV. A proportional odds model that estimated the cumulative probabilities of aGVHD was used to analyze the data using a nonlinear mixed-effects model. Then, the model parameters and plausibility were evaluated by bootstrap and visual predictive checks.

Results: The typical probabilities were 18.9% and 17.9% for grade II and grades III-IV, respectively. The incidence of grade II and grade III-IV aGVHD for human leukocyte antigen (HLA) haplo sibling donor patients was higher than that for HLA-matched donor patients. The incidence of grade II and grade III-IV aGVHD decreased with increasing early cyclosporine trough concentration; however, cyclosporine exposure was not associated with the incidence of aGVHD.

Conclusion: HLA matching and early cyclosporine trough concentration were important factors for the occurrence of aGVHD.

Keywords: acute graft-versus-host disease; cyclosporine; hematopoietic stem cell transplantation; proportional odds model; risk factor.